Imaging brain class I histone deacetylase changes in the Lewy body dementias and Parkinson's disease.

Background: Histone deacetylases (HDACs) are epigenetic molecules responsible for regulation of gene transcription. Altered expression of HDACs has been linked to neurodegenerative disease. Here, we used the class I HDAC PET radioligand [C]Martinostat to quantify and map changes in these molecules in the brain in dementia with Lewy bodies (DLB) and Parkinson's disease (PD).

Development of Carbon-11 Labeled Pyrimidine Derivatives as Novel Positron Emission Tomography (PET) Agents Enabling Brain Sigma-1 Receptor Imaging.

The sigma-1 receptor (σ1R) is a stress-activated chaperone protein that has emerged as a significant therapeutic target for neurodegenerative disorders. Developing effective positron emission tomography (PET) imaging probes targeting σ1R is crucial for visualizing its distribution and function in the brain, as well as facilitating related drug development. In this study, two novel C-labeled PET probes based on the structure of a potent σ1R ligand Lan-0101 are designed and synthesized.

Toward AI-driven neuroepigenetic imaging biomarker for alcohol use disorder: A proof-of-concept study.

Alcohol use disorder (AUD) is a disorder of clinical and public health significance requiring novel and improved therapeutic solutions. Both environmental and genetic factors play a significant role in its pathophysiology. However, the underlying epigenetic molecular mechanisms that link the gene-environment interaction in AUD remain largely unknown.

Acute Effects of Hallucinogens on Functional Connectivity: Psilocybin and Salvinorin-A.

The extent of changes in functional connectivity (FC) within functional networks as a common feature across hallucinogenic drug classes is under-explored. This work utilized fMRI to assess the dissociative hallucinogens Psilocybin, a classical serotonergic psychedelic, and Salvinorin-A, a kappa-opioid receptor (KOR) agonist, on resting-state FC in nonhuman primates. We highlight overlapping and differing influence of these substances on FC relative to the thalamus, claustrum, prefrontal cortex (PFC), default mode network (DMN), and DMN subcomponents.

Preliminary Exploration of Pseudo-CT-Based Attenuation Correction for Simultaneous PET/MRI Brain Imaging in Nonhuman Primates.

This study aimed to develop a template-based attenuation correction (AC) for the nonhuman primate (NHP) brain. We evaluated the effects of AC on positron emission tomography (PET) data quantification with two experimental paradigms by comparing the quantitative outcomes obtained using a segmentation-based AC versus template-based AC. Population-based atlas was generated from ten adult rhesus macaques.

Neurodegenerative Changes in the Brains of the 5xFAD Alzheimer's Disease Model Mice Investigated by High-Field and High-Resolution Magnetic Resonance Imaging and Multi-Nuclei Magnetic Resonance Spectroscopy.

This study aimed to investigate morphological and metabolic changes in the brains of 5xFAD mice. Structural magnetic resonance imaging (MRI) and H magnetic resonance spectroscopy (MRS) were obtained in 10- and 14-month-old 5xFAD and wild-type (WT) mice, while P MRS scans were acquired in 11-month-old mice. Significantly reduced gray matter (GM) was identified by voxel-based morphometry (VBM) in the thalamus, hypothalamus, and periaqueductal gray areas of 5xFAD mice compared to WT mice.

Evaluation of [F]PF-06455943 as a Potential LRRK2 PET Imaging Agent in the Brain of Nonhuman Primates.

Mutations in the leucine-rich repeat kinase 2 (LRRK2) gene are the common causes of inherited Parkinson's disease (PD) and emerged as a causative PD gene. Particularly, LRRK2-Gly2019Ser mutation was reported to alter the early phase of neuronal differentiation, increasing cell death. Selective inhibitors of LRRK2 kinase activity were considered as a promising therapeutic target for PD treatment.

Imaging Leucine-Rich Repeat Kinase 2 In Vivo with F-Labeled Positron Emission Tomography Ligand.

Leucine-rich repeat kinase 2 (LRRK2) has been demonstrated to be closely involved in the pathogenesis of Parkinson's disease (PD), and pharmacological blockade of LRRK2 represents a new opportunity for therapeutical treatment of PD and other related neurodegenerative conditions. The development of an LRRK2-specific positron emission tomography (PET) ligand would enable a target occupancy study in vivo and greatly facilitate LRRK2 drug discovery and clinical translation as well as provide a molecular imaging tool for studying physiopathological changes in neurodegenerative diseases. In this work, we present the design and development of compound (PF-06455943) as a promising PET radioligand through a PET-specific structure-activity relationship optimization, followed by comprehensive pharmacology and ADME/neuroPK characterization.

Development of a new advanced animal cradle for small animal multiple imaging modalities: acquisition and evaluation of high-throughput multiple-mouse imaging.

The physiological conditions of small animals are an essential component to be considered when acquiring images for pre-clinical studies, and they play a vital role in the overall results of a study. However, several previous studies did not consider these conditions. In this study, a new animal cradle that can be modified and adjusted to suit multiple imaging modalities such as positron emission tomography (PET)/computed tomography (CT) and magnetic resonance imaging (MRI) was developed.

An in vivo proton magnetic resonance spectroscopy study with optimized echo-time technique for concurrent quantification and T2 measurement targeting glutamate in the rat brain.

Objective: The present study applied in vivo proton magnetic resonance spectroscopy (H MRS) to concurrently measure the concentration and T2 relaxation time of glutamate with the concept of optimized-for-quantification-and-T2-measurement-of-glutamate (OpQT2-Glu).

Materials And Methods: 7T MRS scans of the OpQT2-Glu were acquired from the prefrontal cortex of five rats. The echo-time-(TE)-specific J-modulation of glutamate was investigated by spectral simulations and analyses for selecting the eight TEs appropriate for T2 estimation of glutamate.

Analysis of ovarian volume of Korean children and adolescents at magnetic resonance imaging.

Background: Knowledge of ovarian volume is important for diagnostic evaluations; however, normal ovarian volume studies on children and adolescents are lacking.

Objective: This study aimed to analyze age-specific ovarian volume and identify the diverse factors that contribute to ovarian diagnoses.

Materials And Methods: We retrospectively enrolled 180 patients (0-18 years of age) with normal ovaries who underwent magnetic resonance imaging (MRI) between 2010 and 2018.

Investigating the metabolic alterations in a depressive-like rat model of chronic forced swim stress: An in vivo proton magnetic resonance spectroscopy study at 7T.

Although recent investigations of major depressive disorder (MDD) have focused on the monoaminergic system, accumulating evidences suggest that alternative pathophysiological models of MDD and treatment options for patients with MDD are needed. Animals subjected to chronic forced swim stress (CFSS) develop behavioral despair. The purpose of this study was to investigate the in vivo effects of CFSS on systems other than the monoamine system in the rat prefrontal cortex (PFC) with 7T and short-echo-time (16.

Metabolic effects of light deprivation in the prefrontal cortex of rats with depression-like behavior: In vivo proton magnetic resonance spectroscopy at 7T.

Recent evidence suggests that the glutamate system plays an important role in the pathogenesis of major depressive disorder (MDD). The aim of this study was to investigate the effects of light deprivation (LD) in the prefrontal cortex (PFC) of animals with depression-like behavior, targeting the glutamate system, using in vivo proton magnetic resonance spectroscopy (H MRS). Male Sprague-Dawley rats were housed in constant darkness for six weeks (n = 12; LD group), while controls (n = 8) were housed under normal light cycles.

Improved quantitative fatty acid values with correction of T2 relaxation time in terminal methyl group: In vivo proton magnetic resonance spectroscopy at ultra high field in hepatic steatosis.

Proton magnetic resonance spectroscopy (MRS) with optimized relaxation time is an effective method to quantify hepatic fatty acid values and characterize steatosis. The aim of this study is to quantify the difference in hepatic lipid content with metabolic changes during the progression of steatosis by using localized MRS sequence with T relaxation time determination. Fatty liver disease was induced in C57BL/6N mice through a high-fat diet (HFD) of pellets containing 60% fat, 20% protein, and 20% carbohydrates.

Decreased Glutamatergic Activity in the Frontal Cortex of Single Prolonged Stress Model: In vivo and Ex Vivo Proton MR Spectroscopy.

Single prolonged stress (SPS) is one of the preclinical models of posttraumatic stress disorder (PTSD) in humans. Not every traumatized person develops PTSD and the onset of the disease varies from months to many years after exposure to life-threatening events. The pathogenetic neurometabolites in PTSD have not been investigated to date, and could provide a means for therapeutic interventions.